Allergology International最新文献

Background: Identification of predictive biomarkers is crucial for formulating preventive interventions and halting the progression of atopic march. Although controversial, the use of accessible markers to predict or detect early onset of atopic diseases is highly desirable. Therefore, this study aimed to investigate whether corneal squamous cell carcinoma antigen-1 (SCCA1) collected from infants can predict the development of atopic dermatitis and food allergy.

Methods: This prospective study enrolled 117 infants aged 2 months (55 female and 62 male infants). The participants were monitored to evaluate the occurrence of eczematous changes at several time points, and stratum corneum samples were obtained. The association of corneal SCCA1 with the development of atopic dermatitis and food allergy in the first 3 years of life was evaluated using univariate and multivariate logistic regression.

Results: The corneal SCCA1 level was significantly higher in children who developed atopic dermatitis than in children who did not (cheek at 2 months: 1653.06 ± 178.48 ng/mg vs. 786.95 ± 101.59 ng/mg, P = 0.0033). The corneal SCCA1 level was also significantly higher in children who developed food allergy than in children who did not (perioral skin at 2 months: 2567.31 ± 408.09 ng/mg vs. 1120.85 ± 188.49 ng/mg, P = 0.0018).

Conclusions: The findings suggest that non-invasive measurements of corneal SCCA1 at 2 months of age is useful for predicting atopic dermatitis and food allergy in infants at risk for atopic dermatitis and subsequent food allergy.

Background: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by an urticaria-like rash and monoclonal gammopathy with fever and fatigue. Although some treatments have shown efficacy in clinical trials, no approved treatment exists. We aimed to assess canakinumab, an anti-IL-1β monoclonal antibody, in Japanese patients.

Methods: This phase II, multicenter, single-arm, open-label study enrolled five patients with active disease from four hospitals. Patients received a single subcutaneous dose of canakinumab 150 mg. The primary endpoint was the proportion of patients achieving a complete clinical response (CR), based on physician global assessment on Day 7. If a CR was not achieved on Day 7 or by 8 weeks post-treatment, the dose was increased to 300 mg. Dosing continued every 8 weeks until 24 weeks. The study also evaluated patient-reported disease activity and changes in acute inflammatory markers, including white blood cell count, neutrophil count, C-reactive protein concentration, and serum amyloid A level. Quality of life was assessed using the Dermatology Life Quality Index and the 36-item Short Form health survey. Safety was also evaluated.

Results: Sixty percent (3/5) of patients had a CR on Day 7. One of the remaining two patients had a CR 7 days after the dose was increased to 300 mg. All five patients, including those who did not achieve a CR, showed improvement in inflammatory markers and quality of life scores, and no new adverse events were detected.

Conclusions: In this trial, canakinumab showed a potential for usefulness in Japanese patients with Schnitzler syndrome.

Background: Patients with asthma-COPD overlap (ACO) have a greater symptom burden, worse respiratory function, and more frequent exacerbations than those with asthma alone. However, only a few studies have investigated the prevalence and clinical course of ACO in severe asthma. This study aimed to examine the comorbid rate of ACO and its clinical impact on severe asthma.

Methods: We prospectively enrolled 127 patients with severe asthma from 30 hospitals and clinics. Favorable treatment adherence was ensured, and the prevalence of ACO was assessed using the Japanese Respiratory Society ACO criteria. Patients were categorized into two groups, ACO and non-ACO, and their clinical characteristics were compared. The exacerbation rates with a 3-year follow-up and the annual change in FEV₁ with a 5-year follow-up of 105 individuals were evaluated. The exacerbation-free rate was analyzed using the Kaplan-Meier method and the Cox proportional hazards model.

Results: The prevalence of ACO in severe asthma was 31.5 %. Patients with ACO were older, more frequently male, and had a longer duration of asthma than those without. No significant difference was observed in exacerbation rates between the ACO and non-ACO groups (62.2 % vs. 63.2 %, P = 0.91) or the annual change in FEV₁ (-39.2 mL/year vs. -31.2 mL/year, P = 0.11).

Conclusions: The prevalence of ACO in our multicenter cohort study on severe asthma was approximately 30 %. The presence of ACO was not an independent risk for exacerbations or decline in FEV₁.

Background: Biologics are integral in the management of severe asthma. As the effectiveness of the anti-IL-5 receptor antibody benralizumab in Japan remains elusive, this study aimed to assess its real-world effectiveness in Japanese patients with severe asthma.

Methods: This prospective, interventional, single-arm clinical trial was conducted across ten facilities in Japan between September 2020 and July 2022. Adult patients with severe eosinophilic asthma (peripheral blood eosinophil count ≥150 cells/μl) were enrolled and treated with benralizumab. The primary endpoint was the change in ACQ-5 score from baseline to week 24.

Results: Of 103 patients, 98 (mean age: 62.1 years, women: 55.1 %, regular oral corticosteroids [OCS] treatment: 20.4 %) were included in the analysis. From baseline to week 24, benralizumab significantly improved ACQ-5 (-0.67, 95 % CI: -0.94 to -0.39) and AQLQ (0.71, 95 % CI: 0.46 to 0.96) scores with an increase in FEV1 (87 ml, 95 % CI: 15-159 ml). The maintenance OCS dose and the percentage of OCS users decreased from 13.9 mg/day to 6.0 mg/day and from 20.4 % to 9.2 %, respectively. Multivariable analysis identified baseline blood eosinophil count (≥400 cells/μl) and fractional exhaled nitric oxide (≥22 ppb) as independent predictors of therapeutic response to benralizumab. Benralizumab treatment was discontinued due to nonserious adverse events and patient choice in four and three patients, respectively.

Conclusions: In a real-world setting in Japan, patients with severe eosinophilic asthma treated with benralizumab demonstrated substantial improvements in asthma control, quality of life, and respiratory function with reduced OCS usage.

Trial registration: Japan Registry of Clinical Trials (jRCTs031190237).

Background: Non-esophageal eosinophilic gastrointestinal diseases (non-EoE EGIDs) are allergic conditions where Th-2-predominant inflammation causes symptoms related to gastrointestinal tract dysfunction. No studies have reported the incidence of non-EoE EGIDs. In addition, little is known about the influence of lifestyle factors on the condition.

Methods: We used a large health claim database from January 2005 to September 2022. Non-EoE EGIDs cases were identified on the basis of the International Classification of Diseases-tenth Revision code, K52.8. The incidence and prevalence of non-EoE EGIDs were estimated by Poisson and binomial distribution, respectively. For each case, 10 controls were randomly selected for a nested case-control study to identify potential risk factors of non-EoE EGIDs.

Results: Of 15,200,895 individuals, 1,368 new cases of non-EoE EGIDs were identified. The incidence and prevalence of non-EoE EGIDs in 2022 were 3.07 (95% CI 2.67-3.52) per 100,000 person-years and 17.23 (95% CI 16.38-18.11) per 100,000 individuals, respectively, which were approximately 6 and 9 times higher than those in 2010. Allergic rhinitis (OR 1.63 (95% CI 1.16-2.29), p = 0.005), chronic sinusitis (OR 2.41 (95% CI 1.58-3.66), p < 0.001), and urticaria (OR 2.32 (95% CI 1.45-3.70), p < 0.001) were related to an increased risk of adult non-EoE EGIDs. Whilst atopic dermatitis (OR 2.28 (95% CI 1.35-3.86), p = 0.006) and the perinatal factors (OR 3.68 (95% CI 1.13-12.02), p = 0.031) were associated with an increased risk of pediatric non-EoE EGIDs. No association was seen with lifestyle factors such as obesity, smoking and alcohol consumption.

Conclusions: The incidence and prevalence of non-EoE EGIDs have increased over the past two decades.

Background: In recent years, the prevalence of allergic rhinitis (AR) in Japanese children has increased significantly. Multiple sensitization and genetic factors are associated with the development of AR, and moreover, multiply sensitized children are more likely to have parents with AR. This research investigated the association of Japanese cedar pollen (JCP) sensitization in children with Dermatophagoides pteronyssinus (DP) sensitization and with maternal JCP sensitization.

Methods: This is an Adjunct Study to the Japan Environment and Children's Study (JECS) in Yamanashi where reports the highest positive rate of JCP sensitization. It included 1469 mother-child pairs who participated in a comprehensive health examination of 8-year-old children (from 2019 to 2022) at the JECS-Yamanashi. Univariate and multivariate logistic regression models were created using the presence/absence of child's JCP sensitization as the objective variable; mother's JCP sensitization and child's DP sensitization as explanatory variables; and child's sex and BMI, mother's age, and JCP exposure in the examination year as adjustment variables.

Results: Children who were positive for DP sensitization were also more likely to be positive for JCP sensitization (adjusted OR: 6.58; 95%CI: 5.10-8.48; P < 0.001). Children who were positive for DP sensitization were also more likely to be positive for JCP sensitization if their mothers were positive for JCP sensitization (adjusted OR: 1.77; 95%CI: 1.16-2.71; P = 0.008).

Conclusions: JCP sensitization is associated with DP sensitization in children. Furthermore, in DP sensitization-positive children, JCP sensitization of the child was associated with JCP sensitization of the mother.

Background: Basophils, despite being the least common granulocytes, play crucial roles in type 2 immune responses, such as chronic allergic inflammation and protective immunity against parasites. However, the molecular mechanisms regulating basophil activation and inflammatory molecule production remain poorly understood. Therefore, we investigated the role of RNA-binding proteins, specifically tristetraprolin (TTP), in regulating inflammatory molecule production in basophils.

Methods: Using antigen/IgE-stimulated basophils from wild-type (WT) and TTP-knockout (TTP-KO) mice, we performed bulk RNA sequencing, transcriptome-wide mRNA stability assays, and protein analyses. We also examined mRNA expression and protein production of inflammatory molecules in TTP-KO basophils under stimulation with IL-33 or LPS. Furthermore, we evaluated the in vivo significance of TTP in basophils using basophil-specific TTP-deficient mice and a hapten oxazolone-induced atopic dermatitis model.

Results: TTP expression was upregulated in basophils following stimulation with antigen/IgE, IL-33, or LPS. Under these stimuli, TTP-KO basophils exhibited elevated mRNA expression of inflammatory molecules, such as Il4, Areg, Ccl3, and Cxcl2, compared to WT basophils. Transcriptome-wide mRNA stability assays revealed that TTP deficiency prolonged the mRNA half-life of these inflammatory mediators. Notably, the production of these inflammatory proteins was significantly increased in TTP-KO basophils. Moreover, basophil-specific TTP-deficient mice showed exacerbated oxazolone-induced atopic dermatitis-like skin allergic inflammation.

Conclusions: TTP is a key regulator of basophil activation, controlling the production of inflammatory mediators through mRNA destabilization. Our in vivo findings demonstrate that the absence of TTP in basophils significantly aggravates allergic skin inflammation, highlighting its potential as a therapeutic target for allergic diseases.